C25-140

C25-140 is a first-in-class small-molecule inhibitor that targets the protein-protein interaction between the E3 ubiquitin ligase tumor necrosis factor receptor-associated factor 6 (TRAF6) and the E2-conjugating enzyme Ubc13 (also known as UBE2N). By disrupting this interaction, C25-140 prevents the generation of Lys63-linked ubiquitin chains, which are essential for the activation of the canonical NF-κB and MAPK signaling pathways. This inhibition suppresses the production of pro-inflammatory cytokines and immune signal propagation. Preclinical studies have demonstrated its potential in treating various inflammatory and autoimmune conditions, including rheumatoid arthritis, psoriasis, acute kidney injury, and neuroinflammatory disorders such as ischemic stroke and intracerebral hemorrhage.